Mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1), a common, widely distributed human genetic disorder that affects approximately 250,000 patients in the US, Europe, and Japan alone. The NF1 gene encodes neurofibromin, a 320 kilodalton protein that functions, at least in part, as a GTPase activating protein (GAP) for p21ras. Neurofibromin is highly conserved among vertebrate species and has high homology with its counterparts, yeast and Drosophila.
Individuals with NF1 exhibit a wide range of malignant and nonmalignant manifestations, including plexiform neurofibromas that collectively affect 25-40% of NF1 patients; these neurofibromas are a major source of life long morbidity and mortality. Given the negative impact that this condition has on people with this mutation and the dearth of effective treatments for this and related condition there is a pressing need for additional treatments for this condition. Various aspects and embodiments disclosed herein address this need.